Light-dependent interaction between Drosophila CRY and the clock protein PER mediated by the carboxy terminus of CRY

Background: The biological clock synchronizes the organism with the environ ment, responding to changes in light and temperature. Drosophila CRYPTOCHRO ME (CRY), a putative circadian photoreceptor, has previously been reported to interact with the clock protein TIMELESS (TIM) in a light-dependent mann er. Although TIM dimerizes with PERIOD (PER), no association between CRY an d PER has previously been revealed, and aspects of the light dependence of the TIM/CRY interaction are still unclear. Results: Behavioral analysis of double mutants of per and cry suggested a g enetic interaction between the two loci. To investigate whether this was re flected in a physical interaction, we employed a yeast-two-hybrid system th at revealed a dimerization between PER and CRY. This was further supported by a coimmunoprecipitation assay in tissue culture cells, We also show that the light-dependent nuclear interactions of PER and TIM with CRY require t he C terminus of CRY and may involve a trans-acting repressor. Conclusions: This study shows that, as in mammals, Drosophila CRY interacts with PER, and, as in plants, the C terminus of CRY is involved in mediatin g light responses. A model for the light dependence of CRY is discussed. (C ) 2001 Elsevier Science Ltd. All rights reserved.